Method of manufacturing a heat transfer element for in vivo cooling

ABSTRACT

An intravascular heat transfer device is provided with a mixing-inducing surface formed by an easily manufacturable process. The device can have a plurality of elongated, articulated segments, each having a mixing-inducing exterior surface. A flexible joint connects adjacent elongated, articulated segments. The device may be conveniently formed, e.g., by vapor deposition or molding, and further lacks undercuts so that the same may be conveniently removed from, e.g., a two-part mold.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.10/117,733, filed on Apr. 4, 2002, now U.S. Pat. No. 6,702,841 entitled“Method Of Manufacturing A Heat Transfer Element For In Vivo Cooling”,which claims priority to U.S. Provisional Patent Application No.60/281,771, filed Apr. 5, 2001, entitled “Mixing-Inducing Heat TransferElement”, and is a continuation-in-part of U.S. patent application Ser.No. 09/607,799, filed Jun. 30, 2000, entitled “Selective Organ CoolingApparatus and Method”, now U.S. Pat. No. 6,464,716, which is acontinuation-in-part of U.S. patent application Ser. No. 09/215,041,filed Dec. 16, 1998, entitled “Articulation Device for Selective OrganCooling Apparatus”, now U.S. Pat. No. 6,254,626; and the presentapplication is also a continuation-in-part of U.S. patent applicationSer. No. 09/379,295, filed Aug. 23, 1999, now abandoned entitled “Methodof Manufacturing a Heat Transfer Element for in Vivo Cooling”, which isa continuation-in-part of Ser. No. 09/103,342, filed Jun. 23, 1998,entitled “Selective Organ Cooling Catheter and Method of Using theSame”, now U.S. Pat. No. 6,096,068, which is a continuation-in-part ofSer. No. 09/047,012, filed Mar. 24, 1998, entitled “Selective OrganHypothermia Method and Apparatus”, now U.S. Pat. No. 5,957,963, which isa continuation-in-part of Ser. No. 09/012,287, filed Jan. 23, 1998,entitled “Selective Organ Hypothermia Method and Apparatus”, now U.S.Pat. No. 6,051,019, all of which are incorporated herein.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to a method for manufacturing aheat transfer element that is capable of modification and control of thetemperature of a body or of a selected body organ. More particularly,the invention relates to a method for manufacturing an intravascularapparatus including a heat transfer element for controlling body andorgan temperature. The invention is also directed to the resulting heattransfer element.

2. Background Information

Organs in the human body, such as the brain, kidney and heart, aremaintained at a constant temperature of approximately 37° C. Hypothermiacan be clinically defined as a core body temperature of 35° C. or less.Hypothermia is sometimes characterized further according to itsseverity. A body core temperature in the range of 33° C. to 35° C. isdescribed as mild hypothermia. A body temperature of 28° C. to 32° C. isdescribed as moderate hypothermia. A body core temperature in the rangeof 24° C. to 28° C. is described as severe hypothermia.

Hypothermia is uniquely effective in reducing brain injury caused by avariety of neurological insults and may eventually play an importantrole in emergency brain resuscitation. Experimental evidence hasdemonstrated that cerebral cooling improves outcome after globalischemia, focal ischemia, or traumatic brain injury. For this reason,hypothermia may be induced in order to reduce the effect of certainbodily injuries to the brain as well as other organs.

Catheters have been developed which are inserted into the bloodstream ofthe patient in order to induce total body hypothermia. For example, U.S.Pat. No. 3,425,419 to Dato describes a method and apparatus of loweringand raising the temperature of the human body. Dato induces moderatehypothermia in a patient using a metallic catheter. The metalliccatheter has an inner passageway through which a fluid, such as water,can be circulated. The Dato catheter has an elongated cylindrical shapeand is constructed from stainless steel. For example, Dato suggests theuse of a catheter approximately 70 cm in length and approximately 6 mmin diameter. It is clear that the Dato device has numerous limitations.For example, such a catheter would likely be inflexible and unable tonavigate a tortuous vasculature.

Cooling helmets or head gear have also been used in an attempt to coolonly the head rather than the patient's entire body. However, suchmethods rely on conductive heat transfer through the skull and into thebrain. One drawback of using conductive heat transfer is that theprocess of reducing the temperature of the brain is prolonged. Also, itis difficult to precisely control the temperature of the brain whenusing conduction due to the temperature gradient that must beestablished externally in order to sufficiently lower the internaltemperature. From a practical standpoint, such devices are cumbersomeand may make continued treatment of the patient difficult or impossible.

Selected organ hypothermia has been accomplished using extracorporealperfusion, as detailed by Arthur E. Schwartz, M.D. et al., in IsolatedCerebral Hypothermia by Single Carotid Artery Perfusion ofExtracorporeally Cooled Blood in Baboons, NEUROSURGERY, vol. 39, no. 3,p. 577 (September, 1996). However, external circulation of blood is nota practical approach for treating humans because the risk of infection,need for anticoagulation, and risk of bleeding is too great.

In all of the above, the devices have tended to have inelegantconstructions, which have neglected some of the subtleties ofhemocompatibility and flexibility. Therefore, a practical method tomanufacture an apparatus, which is capable of modifying and controllingthe temperature of a selected organ, satisfies a long-felt need.

BRIEF SUMMARY OF THE INVENTION

In one aspect, the invention is directed towards a heat transfer devicefor intravascular temperature control of a patient. The device includesa flexible layer of a substantially conductive material, the flexiblelayer having a feature to produce mixing in fluid flowing adjacent thelayer, the flexible layer and feature shaped and configured such thatthe flexible layer may be removed from a multi-part mold in the absenceof an undercut.

Implementations of the invention may include one or more of thefollowing. The fluid may be blood, a working fluid, or both. Theflexible layer may be formed of a metal such as Fe, Ti, Ta, nitinol,stainless steel, Al, Ag, Au, Cu, and Ni, or combinations thereof. Thetotal outside diameter of the device may be between about 6 f to 18 f,and more particularly between about 9 f to 14 f. The heat transferdevice may include heat transfer segments separated by articulatingjoints. The articulating joints may be shaped and configured as bellowsor as flexible tubes. The flexible layer may have a thermal conductivityin the range of about 0.1 to 4 W/cm-K. Each segment may have at leastone feature thereon, the feature including at least two helical ridgesor grooves, one of the at least two helical ridges or grooves havingopposite helicity from another of the helical ridges or grooves.Alternatively, each segment may have a substantially cylindrical shape,the substantially cylindrical shape having a first half-cylinder and asecond half-cylinder, the first and second half-cylinders joined at twosets of parting strips, each parting strip extending substantiallyparallel to an axis of the cylindrical shape; and at least two helicalridges or grooves, one of the at least two helical ridges or groovesdisposed on the first half-cylinder and another disposed on the secondhalf-cylinder. Also alternatively, each segment may have at least onefeature thereon, the feature including a continuous corkscrew design.Alternatively, each segment may have at least one dimple or knobthereon. If at least two features, such dimples or knobs, or acombination thereof, are provided, the same may be are arranged in aline substantially parallel to the axis of the segment. The two may alsobe offset from each other relative to the axis of the segment.

In another aspect, the invention is directed towards a method of makinga heat transfer device. The method includes providing a mold in adeposition apparatus, the mold having an inside shape such that aflexible continuous substantially conductive layer may be deposited inthe mold and shaped, configured, and arranged to have a feature thatcauses mixing in a fluid flowing adjacent the layer.

Implementations of the invention may include one or more of thefollowing. The providing step may further include the step of providinga mold that is shaped, configured, and arranged to form a layer thatlacks undercuts. The feature may include varieties of the featuredisclosed above. The depositing may be performed by a technique selectedfrom the group consisting of CVD, PVD, sputtering, MBE, electroplating,and ECD.

In yet another aspect, the invention is directed towards a productformed by any of the above processes.

In yet a further aspect, the invention is directed towards a method forperforming a medical procedure while managing and controlling thetemperature of the patient. The method includes intravascularlyinserting a catheter having a heat transfer element into a patient to betreated, the heat transfer element being formed of a flexible layer of asubstantially conductive material, the flexible layer having a featureto produce mixing in fluid flowing adjacent the layer, the flexiblelayer and feature shaped and configured such that the flexible layer maybe removed from a multi-part mold in the absence of an undercut; coolingor heating the heat transfer element to control the patient'stemperature; and performing a medical procedure during at least aportion of the time of the cooling or heating step.

Implementations of the invention may include one or more of thefollowing. The medical procedure may be selected from the groupconsisting of: angioplasty, neurosurgery, cardiovascular surgery, stroketreatment, and combinations thereof.

In another aspect, the invention is directed towards a heat transferdevice including a flexible mechanical layer of a metal that is shapedand configured to produce mixing in fluid flowing adjacent the layer,and a biocompatible layer of material disposed adjacent the mechanicallayer.

Implementations of the invention may include one or more of thefollowing. A protective layer may be provided that is formed of amaterial that is not corrosive when exposed to a working fluid, theprotective layer disposed on the side of the mechanical layer oppositethe biocompatible layer. A top layer of a material, chosen from thegroup consisting essentially of heparin, similar antithrombogenicmaterials and lubricious materials, may be disposed on the side of thebiocompatible layer opposite the mechanical layer.

The mechanical layer may be formed of a sandwich structure including atleast two layers of materials. The sandwich structure may be formed oftwo layers of a first material separated by a layer of a secondmaterial. The thickness of all the layers together may be less thanabout 1 mil in thickness. The layers of the first material may each havesubstantially the same thickness. The first material may be selectedfrom the group consisting essentially of Ni, Fe, Ti, steel, Al, or othersimilar materials, or combinations of the same, and the second materialmay be selected from the group consisting essentially of Ag, Au, Cu, orother similar materials, or combinations of the same. The total diameterof the device may be between about 9 french [f] to 14 f. The heattransfer device may include heat transfer segments separated byarticulating joints. The segments may be shaped and configured ashelices and the joints as bellows or flexible tubes. The biocompatiblecoating may be selected from the group consisting essentially of Au,parylene, platinum, other similar materials, and combinations thereof.The mechanical layer may have a thermal conductivity in the range ofabout 0.1 to 4 W/cm-K. A protective layer may be the innermost layer,the protective layer formed of a material which is non-corrosive whenexposed to a working fluid. For working fluids of saline, the protectivelayer may be, e.g., Au.

In another aspect, the invention may be directed to a method of making aheat transfer device, including disposing a mandrel in a depositionapparatus, the mandrel having an outside shape such that a materialformed thereon is configured and arranged to cause mixing in a fluidflowing adjacent the material. Other steps include depositing amechanical layer of a material having sufficient ductility and surfaceenergy to substantially conform to the contours of the outside shape,depositing a biocompatible coating on the mechanical layer, anddissolving the mandrel.

Implementations of the method may include one or more of the following.Either or both of a layer of an antithrombogenic material or alubricious material may be deposited on the biocompatible coating. Aprotective layer may be deposited on the mandrel so as to be theinnermost layer of the device, the protective layer formed of a materialwhich does not corrode when exposed to a working fluid, such as Au. Thebiocompatible coating may be selected from the group consistingessentially of Au, Pt, urethane, Teflon®, other noble metals, parylene,or other similar materials or combinations thereof. The mandrel may beformed of Al, and may be formed having a shape configured and arrangedsuch that a material formed thereon is capable of causing mixing in afluid flowing adjacent the material. The mandrel may be formed by atechnique selected from the group consisting of machining, injectionmolding, laser machining, hydroforming, or other similar techniques. Thesurface of the heat transfer device may be bombarded with nitrogen toprovide a degree of thrombogenicity either in combination with orinstead of an antithrombogenic coating such as heparin. In all of theabove, the depositing may be performed by a technique selected from thegroup consisting of CVD, PVD, sputtering, MBE, electroplating,electrochemical deposition [ECD], or other similar techniques orcombinations of the above. A seed layer may be deposited on the mandrel,the seed layer formed of a material which is capable of bonding to theprotective layer or to the mechanical layer. The depositing a mechanicallayer may include depositing a sandwich structure. The depositing asandwich structure may include depositing a layer of a first metal,depositing a layer of a second metal, and then depositing another layerof the first metal. The first metal may be Ni and the second metal maybe Cu.

Advantages of the invention are manyfold. A highly conductive metallicheat transfer element may be manufactured conveniently. The metallicheat transfer element may retain a high degree of flexibility so as tobe able to navigate tortuous vasculature. The heat transfer element hasan atraumatic profile and is biocompatible.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

The novel features of this invention, as well as the invention itself,will be best understood from the attached drawings, taken along with thefollowing description, in which similar reference characters refer tosimilar parts, and in which:

FIG. 1 is an elevation view of an embodiment of a heat transfer elementaccording to the invention;

FIG. 2 is longitudinal section view of the heat transfer element of FIG.1;

FIG. 3 is a transverse section view of the heat transfer element of FIG.1;

FIG. 4 is a cut-away perspective view of an alternative embodiment of aheat transfer element according to the invention;

FIG. 5 is a transverse section view of the heat transfer element of FIG.4;

FIG. 6 is a schematic representation of layers constituting a wall ofthe heat transfer element according to an embodiment of the inventionand formed by a method according to the invention;

FIG. 7 is a schematic representation of layers constituting a wall ofthe heat transfer element according to a second embodiment of theinvention and formed by a method according to the invention;

FIG. 8 is an exploded schematic representation of layers constituting awall of the heat transfer element according to a third embodiment of theinvention and formed by a method according to the invention;

FIG. 9 is a schematic drawing of a helical groove showing variableindices for determination of optimum construction;

FIG. 10 is a plot of the indices of FIG. 9;

FIG. 11 is a plot showing a segment of a design for a “helical” path;

FIG. 12 is a plot of the projection along the X-view of the path of FIG.11;

FIG. 13 is a plot of the projection along the Y-view of the path of FIG.11;

FIG. 14 is a schematic drawing of an embodiment of a heat transferdevice having helical grooves of different helicities on a singlesegment;

FIG. 15 is a schematic drawing of an embodiment of a heat transferdevice having a dimpled design;

FIG. 16 is another schematic drawing of another embodiment of a heattransfer device having a dimpled design;

FIG. 17 is another schematic drawing of another embodiment of a heattransfer device having a dimpled design;

FIG. 18 is another schematic drawing of another embodiment of a heattransfer device having a dimpled design;

FIGS. 19 and 20 are top and side views of another embodiment of a heattransfer device, this one being especially suited for molding via vapordeposition, inverse hydroforming, or stretchable injection molding;

FIG. 21 is a schematic depiction of a two-part molding forming asubstantially cylindrical heat transfer device;

FIG. 22 is a schematic depiction of a two-part molding forming asubstantially cylindrical heat transfer device that has an undercut;

FIG. 23 is a schematic depiction of a two-part molding forming asubstantially cylindrical heat transfer device that does not have anundercut;

FIG. 24 is schematic drawing of an embodiment of a heat transfer devicehaving a corkscrew design; and

FIGS. 25 and 26 are schematic drawings of an embodiment of a heattransfer device having an empirically determined design having noundercut.

DETAILED DESCRIPTION OF THE INVENTION

In order to regulate the temperature of a selected organintravascularly, a heat transfer element may be placed in the feedingartery of the organ to absorb or deliver heat from or to the bloodflowing into the organ. The transfer of heat may cause either a coolingor a heating of the selected organ. The heat transfer element must besmall enough to fit within the feeding artery while still allowing asufficient blood flow to reach the organ in order to avoid ischemicorgan damage. A heat transfer element that selectively cools an organshould be capable of providing the necessary heat transfer rate toproduce the desired cooling or heating effect within the organ. Byplacing the heat transfer element within the feeding artery of an organ,the temperature of an organ can be controlled without significantlyaffecting the remaining parts of the body. In contrast, by placing theheat transfer element in a large vein, such as the superior vena cava,total body cooling can be effected in a manner which avoids thedeleterious consequences of prior art total body cooling.

To selectively cool the brain, for example, the heat transfer element isplaced into the common carotid artery, or both the common carotid arteryand the internal carotid artery. The internal diameter of the commoncarotid artery ranges from 6 to 8 mm and the length ranges from 80 to120 mm. Thus, the heat transfer element residing in one of thesearteries cannot be much larger than 10 f in diameter in order to avoidoccluding the vessel. For placement in the superior vena cava, the sizeof the heat transfer element may be much larger, e.g., 14 f.

It is important that the heat transfer element be flexible in order tobe placed within the small feeding artery of an organ. Feeding arteries,like the carotid artery, branch off the aorta at various levels.Subsidiary arteries continue to branch off the initial branches. Forexample, the internal carotid artery is a small diameter artery thatbranches off of the common carotid artery near the angle of the jaw.Because the heat transfer element is typically inserted into aperipheral artery, such as the femoral artery, and accesses the feedingartery by initially passing though a series of one or more of thesebranches, the flexibility of the heat transfer element is an importantcharacteristic of the heat transfer element. Further, the heat transferelement is ideally constructed from a highly thermally conductivematerial such as metal in order to facilitate heat transfer. The use ofa highly thermally conductive material increases the heat transfer ratefor a given temperature differential between the coolant within the heattransfer element and the blood. This facilitates the use of a highertemperature coolant within the heat transfer element, allowing safercoolants, such as water, to be used. Highly thermally conductivematerials, such as metals, tend to be rigid. Therefore, the design ofthe heat transfer element should facilitate flexibility in an inherentlyinflexible material. More details of the construction of the heattransfer element are disclosed below.

In order to obtain the benefits of hypothermia described above, it isdesirable to reduce the temperature of the blood flowing to the brain(or alternatively for total body cooling, to the blood flowing out ofthe heart) to between 30° C. and 32° C. Given that a typical brain has ablood flow rate through each carotid artery (right and left) ofapproximately 250–375 cubic centimeters per minute, the heat transferelement should absorb 75–175 Watts of heat when placed in one of thecarotid arteries, in order to induce the desired cooling effect. Itshould be noted that smaller organs may have less blood flow in thesupply artery and may require less heat transfer, such as 25 Watts. Fortotal body cooling, rates of 250–300 Watts may be required.

The magnitude of the heat transfer rate is proportional to the surfacearea of the heat transfer element, the temperature differential, and theheat transfer coefficient of the heat transfer element.

As noted above, the receiving vessel into which the heat transferelement is placed has a limited diameter and length. Thus, surface areaof the heat transfer element must be limited, to avoid significantobstruction of the vessel, and to allow the heat transfer element topass easily through the vascular system. For placement within theinternal and common carotid artery, the cross sectional diameter of theheat transfer element is limited to about 4 mm, and its length islimited to approximately 10 cm. Other vessels may have differentrequirements. For example, for placement within the superior vena cavato effect total body cooling, the cross sectional diameter of the heattransfer element may be considerably larger, e.g., 12 f, 14 f, 16 f, 18f, 20 f, or even more.

The mechanisms by which the value of the convection heat transfercoefficient may be increased are complex. However, it is known that theconvection heat transfer coefficient increases with the level ofturbulent kinetic energy in the fluid flow. Thus it is advantageous tohave turbulent blood flow in contact with the heat transfer element. Forreasons given in the parent cases of this application, turbulent flow,or at least mixing flow, can be induced using surface features on theheat transfer element. This flow can be induced both in the blood and inthe working fluid. The surface features may be, as disclosed below,counter-rotating helices, non-counter-rotating helices, staggered ornon-staggered protuberances, etc.

In particular, to create the desired level of mixing intensity in theblood, one embodiment of the invention uses a modular design. Thisdesign creates helical blood flow and produces a high level of mixing inthe free stream by periodically forcing abrupt changes in the directionof the helical blood flow. FIG. 1 is a side view of such a mixinginducing heat transfer element which may be employed within an artery orvein. The abrupt changes in flow direction are achieved through the useof a series of two or more heat transfer segments, each comprised of oneor more helical ridges.

The use of periodic abrupt changes in the helical direction of the bloodflow in order to induce mixing may be illustrated with reference to acommon clothes washing machine. The rotor of a washing machine spinsinitially in one direction causing laminar flow. When the rotor abruptlyreverses direction, significant kinetic energy is created within thewash basin as the changing currents cause random mixing motion withinthe clothes-water slurry.

Referring to FIG. 1, the heat transfer element 14 is comprised of aseries of elongated, articulated segments or modules 20, 22, 24. Threesuch segments are shown in this embodiment, but two or more suchsegments could be used without departing from the spirit of theinvention. As seen in FIG. 1, a first elongated heat transfer segment 20is located at the proximal end of the heat transfer element 14. Amixing-inducing exterior surface of the segment 20 comprises fourparallel helical ridges 28 with four parallel helical grooves 26therebetween. One, two, three, or more parallel helical ridges 28 couldalso be used without departing from the spirit of the present invention.In this embodiment, the helical ridges 28 and the helical grooves 26 ofthe heat transfer segment 20 have a left-hand twist, referred to hereinas a counter-clockwise spiral or helical rotation, as they proceedtoward the distal end of the heat transfer segment 20.

The first heat transfer segment 20 is coupled to a second elongated heattransfer segment 22 by a first bellows section 25, which providesflexibility and compressibility. The second heat transfer segment 22comprises one or more helical ridges. 32 with one or more helicalgrooves 30 therebetween. The ridges 32 and grooves 30 have a right hand,or clockwise, twist as they proceed toward the distal end of the heattransfer segment 22. The second heat transfer segment 22 is coupled to athird elongated heat transfer segment 24 by a second bellows section 27.The third heat transfer segment 24 comprises one or more helical ridges36 with one or more helical grooves 34 therebetween. The helical ridge36 and the helical groove 34 have a left hand, or counter-clockwise,twist as they proceed toward the distal end of the heat transfer segment24. Thus, successive heat transfer segments 20, 22, 24 of the heattransfer element 14 alternate between having clockwise andcounterclockwise helical twists. The actual left or right hand twist ofany particular segment is immaterial, as long as adjacent segments haveopposite helical twists.

In addition, the rounded contours of the ridges 28, 32, 36 also allowthe heat transfer element 14 to maintain a relatively atraumaticprofile, thereby minimizing the possibility of damage to the bloodvessel wall. A heat transfer element according to the present inventionmay be comprised of one, two, three, or more heat transfer segments.

The bellows sections 25, 27 are formed from seamless and nonporousmaterials, such as metal, and therefore are impermeable to gas, whichcan be particularly important, depending on the type of working fluidwhich is cycled through the heat transfer element 14. The structure ofthe bellows sections 25, 27 allows them to bend, extend and compress,which increases the flexibility of the heat transfer element 14 so thatit is more readily able to navigate through blood vessels. The bellowssections 25, 27 also provide for axial compression of the heat transferelement 14, which can limit the trauma when the distal end of the heattransfer element 14 abuts a blood vessel wall. The bellows sections 25,27 are also able to tolerate cryogenic temperatures without a loss ofperformance. The bellows sections may be replaced with flexible tubes orthin-walled metal or polymers. In an alternative embodiment, the bellowsmay be replaced by helical springs which are then coated with a polymerto make a fluid-tight seal. As it is believed that the majority of theheat transfer is through the heat transfer segments, as opposed to thebellows, such an embodiment would be unlikely to unduly affect the heattransfer.

FIG. 2 is a longitudinal sectional view of the heat transfer element 14of an embodiment of the invention, taken along line 2—2 in FIG. 1. Someinterior contours are omitted for purposes of clarity. An inner tube 42creates an inner coaxial lumen 40 and an outer coaxial lumen 46 withinthe heat transfer element 14. Once the heat transfer element 14 is inplace in the blood vessel, a working fluid such as saline or otheraqueous solution may be circulated through the heat transfer element 14.Fluid flows up a supply catheter into the inner coaxial lumen 40. At thedistal end of the heat transfer element 14, the working fluid exits theinner coaxial lumen 40 and enters the outer lumen 46. As the workingfluid flows through the outer lumen 46, heat is transferred from theworking fluid to the exterior surface 37 of the heat transfer element14. Because the heat transfer element 14 is constructed from a highconductivity material as explained in more detail below, the temperatureof its exterior surface 37 may reach very close to the temperature ofthe working fluid. The tube 42 may be formed as an insulating divider tothermally separate the inner lumen 40 from the outer lumen 46. Forexample, insulation may be achieved by creating longitudinal airchannels in the wall of the insulating tube 42. Alternatively, theinsulating tube 42 may be constructed of a non-thermally conductivematerial like polytetrafluoroethylene or another similar polymer.

It is important to note that the same mechanisms that govern the heattransfer rate between the exterior surface 37 of the heat transferelement 14 and the blood also govern the heat transfer rate between theworking fluid and the interior surface 38 of the heat transfer element14. The heat transfer characteristics of the interior surface 38 areparticularly important when using water, saline or other fluid whichremains a liquid as the coolant. Other coolants, such as freon, undergonucleate boiling and create mixing through a different mechanism. Salineis a safe coolant because it is non-toxic, and leakage of saline doesnot result in a gas embolism, which could occur with the use of boilingrefrigerants. Since mixing in the coolant is enhanced by the shape ofthe interior surface 38 of the heat transfer element 14, the coolant canbe delivered to the heat transfer element 14 at a warmer temperature andstill achieve the necessary heat transfer rate.

This has a number of beneficial implications in the need for insulationalong the catheter shaft length. Due to the decreased need forinsulation, the catheter shaft diameter can be made smaller. Theenhanced heat transfer characteristics of the interior surface of theheat transfer element 14 also allow the working fluid to be delivered tothe heat transfer element 14 at lower flow rates and lower pressures.High pressures may make the heat transfer element 14 stiff and cause itto push against the wall of the blood vessel, thereby shielding part ofthe exterior surface 37 from the blood. Because of the increased heattransfer characteristics achieved by the alternating helical ridges 28,32, 36, the pressure of the working fluid may be as low as 5atmospheres, 3 atmospheres, 2 atmospheres or even less than 1atmosphere.

FIG. 3 is a transverse sectional view of the heat transfer element 14according to an embodiment of the invention, taken at a location denotedby the line 3—3 in FIG. 1. FIG. 3 illustrates a five-lobed embodiment,whereas FIG. 1 illustrates a four-lobed embodiment. As mentionedearlier, any number of lobes might be used. In FIG. 3, the coaxialconstruction of the heat transfer element 14 is clearly shown. The innercoaxial lumen 40 is defined by the insulating coaxial tube 42. The outerlumen 46 is defined by the exterior surface of the insulating coaxialtube 42 and the interior surface 38 of the heat transfer element 14. Inaddition, the helical ridges 32 and helical grooves 30 may be seen inFIG. 3.

As noted above, in the preferred embodiment, the depth of the grooves,d_(i), may be greater than the boundary layer thickness which would havedeveloped if a cylindrical heat transfer element were introduced. Forexample, in a heat transfer element 14 with a 4 mm outer diameter, thedepth of the invaginations, d_(i), may be approximately equal to 1 mm ifdesigned for use in the carotid artery.

Although FIG. 3 shows four ridges and four grooves, the number of ridgesand grooves may vary. Thus, heat transfer elements with 1, 2, 3, 4, 5,6, 7, 8 or more ridges are specifically contemplated.

Referring back to FIG. 1, the heat transfer element 14 has been designedto address all of the design criteria discussed above. First, the heattransfer element 14 is flexible and is made of a highly conductivematerial. The flexibility is provided by a segmental distribution ofbellows sections 25, 27 that provide an articulating mechanism. Bellowshave a known convoluted design that provides flexibility. Second, theexterior surface area 37 has been increased through the use of helicalridges 28, 32, 36 and helical grooves 26, 30, 34. The ridges also allowthe heat transfer element 14 to maintain a relatively atraumaticprofile, thereby minimizing the possibility of damage to the vesselwall. Third, the heat transfer element 14 has been designed to promoteturbulent kinetic energy both internally and externally. The modular orsegmental design allows the direction of the invaginations to bereversed between segments. The alternating helical rotations create analternating flow that results in mixing the blood in a manner analogousto the mixing action created by the rotor of a washing machine thatswitches directions back and forth. This mixing action is intended topromote high level turbulent kinetic energy to enhance the heat transferrate. The alternating helical design also causes beneficial mixing, orturbulent kinetic energy, of the working fluid flowing internally.

FIG. 4 is a cut-away perspective view of an alternative embodiment of aheat transfer element 50. An external surface 52 of the heat transferelement 50 is covered with a series of axially staggered protrusions 54.The staggered nature of the outer protrusions 54 is readily seen withreference to FIG. 5 which is a transverse cross-sectional view taken ata location denoted by the line 5—5 in FIG. 4. In order to induce freestream mixing, the height, d_(p), of the staggered outer protrusions 54may be greater than the thickness of the boundary layer which woulddevelop if a smooth heat transfer element had been introduced into theblood stream. As the blood flows along the external surface 52, itcollides with one of the staggered protrusions 54 and a turbulent wakeflow is created behind the protrusion. As the blood divides and swirlsalong side of the first staggered protrusion 54, its turbulent wakeencounters another staggered protrusion 54 within its path preventingthe re-lamination of the flow and creating yet more mixing. In this way,the velocity vectors are randomized and mixing is created not only inthe boundary layer but also in at least a portion of the free stream. Asis the case with the preferred embodiment, this geometry also induces amixing effect on the internal coolant flow.

In use, a working fluid is circulated up through an inner coaxial lumen56 defined by an insulating coaxial tube 58 to a distal tip of the heattransfer element 50. The working fluid then traverses an outer coaxiallumen 60 in order to transfer heat to the exterior surface 52 of theheat transfer element 50. The inside surface of the heat transferelement 50 is similar to the exterior surface 52 in order to inducemixing flow of the working fluid. The inner protrusions can be alignedwith the outer protrusions 54, as shown in FIG. 5, or they can be offsetfrom the outer protrusions 54, as shown in FIG. 4.

The heat transfer element can absorb or provide over 75 Watts of heat tothe blood stream and may absorb or provide as much as 100 Watts, 150Watts, 170 Watts, 250 Watts, 300 Watts, or more. For example, a heattransfer element with a diameter of 4 mm and, a length of approximately10 cm using ordinary saline solution chilled so that the surfacetemperature of the heat transfer element is approximately 5° C. andpressurized at 2 atmospheres can absorb about 100 Watts of energy fromthe bloodstream. Smaller geometry heat transfer elements may bedeveloped for use with smaller organs which provide 60 Watts, 50 Watts,25 Watts or less of heat transfer.

The method of manufacturing a heat transfer element will now bedescribed in more detail. The exterior structure of the heat transferelement is of a complex shape as has been described in order to inducemixing in the flow of blood around the heat transfer element, as well asto induce mixing in the flow of working fluid within the heat transferelement. As may be clear, many varieties and shapes may be employed tocause such flow. Such shapes are termed herein as “mixing-inducingshapes”. Examples of mixing-inducing shapes include: helical,alternating helical or other enantiomorphic shapes, aberration-includingshapes, bump-including shapes, channel-including shapes, crenellatedshapes, hook- or horn- shapes, labyrinthine shapes, and any other shapescapable of inducing mixing. Thus, the metallic element or elements orcompounds forming the heat transfer element must be sufficiently ductileto assume such shapes during deposition.

It is further noted here that while the generic term “deposition” isused, this term is intended broadly to cover any process in which metalsor coating may be disposed on a mandrel or other layer of a heattransfer element. For example, deposition may include: CVD, PVD,sputtering, MBE, forms of crystal or amorphic material “growth”, spraycoating, electroplating, ECD, and other methods which may be employed toform a mandrel or a coating having a mixing-inducing shape. Methods suchas ECD and electroplating have the benefit of having a chargedworkpiece—this charge may be employed to fix the workpiece to the tool.

In general, the processes which may be employed to form the heattransfer element include forming a mandrel having a mixing inducingshape, coating the mandrel with a metal layer or a series of layers(i.e., the heat transfer element), and dissolving the mandrel.

A first step in the process of forming a heat transfer element may be toform a mandrel. One type of mandrel may be made of aluminum such as Al6061 with a T6 heat treatment. Aluminum is useful because the same iscapable of being dissolved or leached out easily with a caustic soda. Ahole disposed along the axis of the heat transfer element may speed suchleaching. The mandrel may be formed by machining such as by a CitizenSwiss Screw Machine. The mandrel may also be made via injection moldingif the same is made of plastic, wax, low-melting-temperaturethermoplastics, and the like. Other methods which may be employed toform the mandrel include machining via laser (note that laser forming istypically only employed for the outside of an element), hydroforming,and other similar methods.

However the mandrel is formed, it is important for the same to have asmooth surface finish and exterior texture. In this way, the resultingheat transfer element will be smooth. A smooth mandrel allows anatraumatic device to be formed around the same. A smooth mandrel alsoallows a smooth metallic coating (heat transfer element) to be simplydeposited around the same thus ensuring uniform heat transfer, aconstant thickness of biocoating, an atraumatic profile, etc.

A basic series of coating layers is shown in FIG. 6. FIG. 6 shows amechanical layer 104, typically made of a metal, and a biocompatiblelayer 106. The mechanical layer 104 is the basic conductive element. Themechanical layer 104 is responsible for heat conduction to providecooling and thus should have a thermal conductivity in the range ofabout 0.1 to 4 W/cm-K, so long as such materials can be deposited.Typical metals which may be employed for the mechanical layer 104include Ni, Cu, Au, Ag, Ti, Ta, nitinol, stainless steel, etc. orcombinations of these or other similar elements. The thickness of themechanical layer should be less than about 2 mils thick to allow forsufficient flexibility to navigate tortous vasculature, although this isstrongly dependent on the type of metal and on the tortuousity of thevasculature involved. Regarding the type of metal, any noble metal maybe employed. Certain of these have deleterious biocompatibility,however, and each has different manufacturing concerns. For example, aAu heat transfer element would require a seed layer since Au will notstick to the Al mandrel.

Ni has been found to be useful. Cu is also useful and has a highconductivity; unfortunately, Cu is also likely to assume the form of thevasculature in which the same is disposed.

For sake of argument, it is assumed here that Ni forms the basic heattransfer element. As stated above, Ni is not hemocompatible. Thus, abiocompatible layer 106 is disposed on the mechanical layer 104 as isshown in FIG. 6. The biocompatible layer may be, e.g., urethane,parylene, Teflon®, a lubricious coating, an antithrombogenic coatingsuch as heparin, a noble metal such as Au, or combinations of the aboveor other similar materials.

One difficulty with the above embodiment may be that, with use ofcertain working fluids, such as saline, corrosion of the mechanicallayer may occur. In the case of a mechanical layer 104 of Ni, saline maybe especially corrosive. Thus, a protective layer 102 may be employedthat is noncorrosive with respect to saline. For example, the protectivelayer 102 may be made of Au. A Au protective layer 102 may encounterdifficulties attaching to an aluminum mandrel, and thus if necessary alayer of Cu may be deposited on the mandrel prior to deposition of theAu layer. Following the dissolution of the mandrel, the Cu layer mayalso be etched away. The protective layer may generally be any noble orinert metal, or may be a polymer or other protective material such asTeflon®.

Alternatively, the protective layer 102 may be vacuum deposited, such asby a vapor deposition method, following removal or dissolution of themandrel. The resulting hole left by the dissolved mandrel allows a pathfor vaporized gases or liquid chemicals to flow. Thus, materials can bedeposited in this fashion on the inside of the heat transfer element.The materials so deposited may be the same as those discussed above:polymers, such as non-corrosive or non-polar polymers, noble metals, andthe like.

FIG. 7 also shows two layers above the mechanical layer 104: abiocompatible layer 106 and a heparin/lubricious layer 108. These mayalso be combined to form a single biocompatible layer. Alternatively,the biocompatible layer may be a “seed” layer which enhances theconnection of the heparin/lubricious layer 108 to the underlyingmechanical layer 104. Such a seed layer may be, e.g., parylene. Finally,it should be noted that the heparin/lubricious layer 108 is indicated asexemplary only: either heparin or a lubricious layer may be depositedindividually or in combination. For example, in certain applications,heparin may not be necessary.

Another embodiment is shown in FIG. 8. This embodiment addresses anotherdifficulty that may occur with various metals. For example, a mechanicallayer 104 that is made entirely of Ni may have too low a burst pressure,partially due to its porosity. The protective layer 102 of FIG. 7 mayaddress some of these concerns. A better approach may be that shown inFIG. 8. In FIG. 8, the mechanical layer 104 is broken up into severallayers. Two, three, or more layers may be employed. In FIG. 8, layers104 a and 104 care formed of a first material such as Ni. An interiorlayer 104 b is deposited between layers 104 a and 104 c. This layer 104b may be formed of a second material such as Cu. This combination oflayers 104 a, 104 b, and 104 c forms a mechanical “sandwich” structure.The Cu layer 104 b (the second “metal” or “layer”) may serve to close“pinholes” that may exist within the more porous Ni layers 104 a and 104c (the first “metal” or “layer”).

One embodiment that has been found useful is that described by Table Ibelow. In Table I, the biocompatible coating is a noble metal layer ofAu. It should be noted that Table I describes a very specific embodimentand is provided purely for illustrative purposes. Table I should not beconstrued as limiting. Table I is keyed to FIG. 8.

Layer Number Material Thickness 102 Au (e.g., 1/10 mil mil-g-45204, typeone, grade A, class one) 104a Ni 3½/10 to 1 mil 104b Cu 1/10 mil 104c Ni3½/10 to 1 mil 106 Au 1/10 mil 108 heparin/ 7–10 microns lubricious

The overall thickness of the group of layers 102–108 may be about 1 mil.The nickel and copper may contain traces of other elements withoutdeleterious consequences.

In some cases, the heat transfer device may be constructed using amulti-part mold, and in particular a two-part mold. The difficulty inthis case may often be the removal of the device from the two-part mold,especially with respect to more convoluted features, such as helicalgrooves, which may often get “caught” on a section of the mold and arethus rendered unremovable. This “catching” typically occurs in thecontext of an undercut.

For example, referring to FIG. 21, a multi-part mold 300 isschematically shown having an interior wall 302. A part 304 is shownwithin the mold. These shapes are to be construed generally—the part 304and wall 302 may well have features that are convoluted, such as ridgesor grooves or both, or dimples or knobs or both, etc.

Referring now to FIG. 22, a mold 300 is shown that creates an undercutin a part 304. In particular, interior wall 302 has a section 306 thatcreates a feature 308 in the part or heat transfer element 304. Here,“part” is intended to refer to a heat transfer element or a heattransfer segment, depending on context. In FIG. 22, the part 304 has anundercut, in particular at section 308, because the part 304 cannot belifted up, in the direction indicated by arrow 310, without having thefeature 308 “catch” on section 306. While the part may be maneuvered insuch a way to remove the same from the mold, such practices areinconvenient and do not transfer well to large scale manufacturing.

Referring now to FIG. 23, a mold 300′ is shown that creates a featurebut not an undercut in a part 304′. In particular, an interior wall 302′of mold 300′ has a section 306′ that creates a feature 308′ in the partor heat transfer element 304′. In FIG. 23, the part 304′ does not havean undercut because the part 304′ can be lifted up, in the directionindicated by arrow 310, without having the feature 308′ “catch” onsection 306′.

In an embodiment of the invention, and referring to FIG. 9, amathematical construct is employed to find a helical groove design thatcan be more easily and reliably removed from a multi-part groove. Usingtwo helical grooves with initial and terminal points at 180° intervalsaround the circumference of a cylinder, some combination of (φ, w, δ)should allow the resulting device to be removable from a 2-part mold. InFIG. 9, the “parting” line of the mold would be the plane of the page.

Referring to FIG. 10, an empirical exploration of the parameter space isshown. By studying this parameter space, the locus of points (φ, w, δ)should be revealed for a device that has no undercut.

As noted above, the heat transfer element employs a helical groove toimpart angular momentum to the external flow, resulting in enhancedmixing and increased heat transfer relative to that which would obtainwith a smoother cylindrical part. And as noted, in some embodiments, thehelical groove may have pitch and depth such that its manufacture isless convenient using a 2-part mold (i.e., a mold with two halves). Byrelaxing the constraint on pitch (i.e. reducing pitch) and reducing thenumber of leads (number of distinct helices), a 2-lead helical segmentwith minimal undercut can be designed which may be compatible with a2-part molding process.

If the constraint of a purely helical groove is removed, then alternateforms may be manufactured using a 2-part mold, e.g., with pitch varyingalong the length of the groove.

For example, an ellipse may describe the intersection of a circularcylinder and a plane. If a sequence of similar ellipses, allcircumscribed around the same right circular cylinder, are constructedsuch that they intersect at the termini of their major axes, then bytraversing alternate halves of subsequent ellipses, a path along thelength of the cylinder is obtained which contains co-planar pointsthrough each of which may be drawn a line normal to the axis of thecylinder. A short segment of the resulting (3-D) path is shown in FIG.11. Projections of this path along the directions indicated as ‘X-view’and ‘Y-view’ are shown in FIGS. 12 and 13, respectively. If the pathshown in FIG. 11 represents the (bottom) vertex of a triangular groovemachined into a larger circular cylinder, then a unique plane parallelto the plane of FIG. 12 and containing the axis of the cylinder may bedefined which divides the cylinder into two halves. Since the groove isnormal to the plane at the corresponding intersection (of groove andplane), each of the resulting halves may be consistent with themanufacture of the grooved cylinder using a 2-part mold. The region ofthe space (φ, w, δ) where φ is the angle of the major axes of theellipses relative to the cylinder axis, and w and ,δ are the width anddepth, respectively, of the groove defined by path shown in FIG. 11,containing grooves which are compatible with a 2-part mold has not beendetermined. In any case, the relaxation of the constraint of a purelyhelical path allows construction of a more easily manufactured partwhich has on at least part of its surface a groove with sufficient pitchto enhance mixing and heat transfer.

In FIG. 25, and the more detailed view thereof in FIG. 26, a part 500 isshown with ridges 502 and grooves 504 that are empirically believed toprovide such heat transfer, and yet be easily removed from a mold.

Other geometries may also be advantageously employed. For example, theabove-mentioned embodiments generally show either all of the helicalsegments having either a left or right hand helical sweep per segment.Referring to FIG. 14, a design is shown that incorporates both left(202) and right (204) hand helical sweeps into one segment 200. Thisdesign may improve fluid turbulence internally as well as externally. Ofcourse, it will be noted that pitch and the number of revolutions forthese particular segments can be changed for different variations.Another possible segment for use with the heat transfer element could bea dimpled design heat transfer element 206, as shown in FIG. 15. In thisembodiment, a number of dimples 208 are shown. The turbulence internallyand externally may be improved in this design.

In a related embodiment, as shown in FIG. 16, a heat transfer segment210 has a series of dimples 212 arranged in a straight line, parallel tothe axis of the segment.

In another related embodiment, the dimples may be inverted to form knobs214, as shown in the heat transfer segment 216 of FIG. 17. The knobs mayalso be arranged in a straight line, parallel to the axis of thesegment, as shown by knobs 220 of segment 218 in FIG. 18. The knobbeddesigns may tend to especially increase turbulence externally. They mayalso tend to reduce the likelihood of thrombosis.

FIGS. 19 and 20 show two views, a top and side view, respectively, of ahelical segment 220 that is especially capable of being molded by vapordeposition techniques or by inverse hydroforming or by stretchableinjection molding (2 mold halves). In this embodiment, the segment 220has a substantially cylindrical shape with helical features thereon, andthe substantially cylindrical shape has a first half-cylinder 221 and asecond half-cylinder 223. The first and second half-cylinders are joinedat two sets of parting strips, of which only one, denoted 222, is shown.Each parting strip extends substantially parallel to an axis of thecylindrical shape. One set of helical ridges 224 or grooves 226, or both(as shown), are disposed on the first half-cylinder and another isdisposed on the second half-cylinder.

As seen by the top of FIG. 20, the parting strip 222 is employed toserve as the location adjacent to which the two mold halves cometogether. In this way, all of the helical invaginations, formed byridges 224 and grooves 226, may be formed without any undercut, therebyminimizing the difficulty of removing the segment from the mold. Ofcourse, it will be seen that the “helical” grooves and ridges alwayssubtend an angle of less than 180°, as none extends all the way aroundthe segment. Such discontinuities may help to increase the overallamount of mixing or turbulence created. An additional advantage is thatthe distal 230 and proximal 228 ends may be more easily coupled toadjoining segments or joints (not shown).

A further embodiment is shown in FIG. 24. In this embodiment, a heattransfer segment 400 of a heat transfer element is shown. Heat transfersegment 400 has a “corkscrew” design, in which the helical ridge 402 andgroove 404 forms a continuous ridge and groove from the proximal end 406of the segment to the distal end 408.

While the particular invention as herein shown and disclosed in detailis fully capable of obtaining the objects and providing the advantageshereinbefore stated, it is to be understood that this disclosure ismerely illustrative of the presently preferred embodiments of theinvention and that no limitations are intended other than as describedin the appended claims.

1. A heat transfer device for intravascular temperature control of apatient, comprising: a flexible layer of a material, the flexible layerhaving a feature to produce mixing in fluid flowing adjacent said layer,the flexible layer and feature shaped and configured such that theflexible layer may be removed from a multi-part mold in the absence ofan undercut, wherein the heat transfer device includes heat transfersegments separated by articulating joints.
 2. The device of claim 1,wherein the flexible layer is formed of a metal selected from the groupconsisting essentially of Fe, Ti, Ta, nitinol, stainless steel, Al, Ag,Au, Cu, and Ni.
 3. The device of claim 1, wherein a total outsidediameter of the device is between about 9 f to 18 f.
 4. The device ofclaim 1, wherein the articulating joints are shaped and configured asbellows.
 5. The device of claim 1, wherein the articulating joints areshaped and configured as flexible tubes.
 6. The device of claim 1,wherein the flexible layer has a thermal conductivity in the range ofabout 0.1 to 4 W/cm-K.
 7. The device of claim 1, wherein each segmenthas at least one feature thereon, the feature including at least twohelical ridges or grooves, one of said at least two helical ridges orgrooves having opposite helicity from another of said helical ridges orgrooves.
 8. The device of claim 1, wherein each segment has asubstantially cylindrical shape, said substantially cylindrical shapehaving a first half-cylinder and a second half-cylinder, said first andsecond half-cylinders joined at two sets of parting strips, each partingstrip extending substantially parallel to an axis of the cylindricalshape; and at least two helical ridges or grooves, one of said at leasttwo helical ridges or grooves disposed on the first half-cylinder andanother disposed on the second half-cylinder.
 9. The device of claim 1,wherein each segment has at least one feature thereon, the featureincluding a continuous corkscrew design.
 10. The device of claim 1,wherein each segment has at least one dimple or knob thereon.
 11. Thedevice of claim 10, wherein each segment has at least two featuresthereon, the at least two features being selected from the groupconsisting of dimples or knobs or combinations thereof.
 12. The deviceof claim 11, wherein the at least two features are arranged in a linesubstantially parallel to the axis of the segment.
 13. The device ofclaim 11, wherein the at least two features are arranged to be not in aline substantially parallel to the axis of the segment.
 14. A method forperforming a medical procedure while managing and controlling thetemperature of the patient, comprising: intravascularly inserting acatheter having a heat transfer element into a patient to be treated,the heat transfer element being formed of a flexible layer of amaterial, the flexible layer having a feature to produce mixing in fluidflowing adjacent said layer, the flexible layer and feature shaped andconfigured such that the flexible layer may be removed from a multi-partmold in the absence of an undercut; and cooling or heating the heattransfer element to control the patient's temperature.
 15. The method ofclaim 14, wherein the medical procedure is selected from the groupconsisting of: angioplasty, neurosurgery, cardiovascular surgery, stroketreatment, and combinations thereof.
 16. The device of claim 1, whereinthe fluid is blood.
 17. The device of claim 1, wherein the fluid is aworking fluid.